The increase of the functional entropy of the human brain with age

We use entropy to characterize intrinsic ageing properties of the human brain. Analysis of fMRI data from a large dataset of individuals, using resting state BOLD signals, demonstrated that a functional entropy associated with brain activity increases with age. During an average lifespan, the entropy, which was calculated from a population of individuals, increased by approximately 0.1 bits, due to correlations in BOLD activity becoming more widely distributed. We attribute this to the number of excitatory neurons and the excitatory conductance decreasing with age. Incorporating these properties into a computational model leads to quantitatively similar results to the fMRI data. Our dataset involved males and females and we found significant differences between them. The entropy of males at birth was lower than that of females. However, the entropies of the two sexes increase at different rates, and intersect at approximately 50 years; after this age, males have a larger entropy

Temporal bacterial and metabolic development of the preterm gut reveals specific signatures in health and disease

Background - The preterm microbiome is crucial to gut health and may contribute to necrotising enterocolitis (NEC), which represents the most significant pathology affecting preterm infants. From a cohort of 318 infants, <32 weeks gestation, we selected 7 infants who developed NEC (defined rigorously) and 28 matched controls. We performed detailed temporal bacterial (n = 641) and metabolomic (n = 75) profiling of the gut microbiome throughout the disease. Results - A core community of Klebsiella, Escherichia, Staphyloccocus, and Enterococcus was present in all samples. Gut microbiota profiles grouped into six distinct clusters, termed preterm gut community types (PGCTs). Each PGCT reflected dominance by the core operational taxonomic units (OTUs), except of PGCT 6, which had high diversity and was dominant in bifidobacteria. While PGCTs 1–5 were present in infants prior to NEC diagnosis, PGCT 6 was comprised exclusively of healthy samples. NEC infants had significantly more PGCT transitions prior to diagnosis. Metabolomic profiling identified significant pathways associated with NEC onset, with metabolites involved in linoleate metabolism significantly associated with NEC diagnosis. Notably, metabolites associated with NEC were the lowest in PGCT 6. Conclusions - This is the first study to integrate sequence and metabolomic stool analysis in preterm neonates, demonstrating that NEC does not have a uniform microbial signature. However, a diverse gut microbiome with a high abundance of bifidobacteria may protect preterm infants from disease. These results may inform biomarker development and improve understanding of gut-mediated mechanisms of NEC

Anti-nausea effects and pharmacokinetics of ondansetron, maropitant and metoclopramide in a low-dose cisplatin model of nausea and vomiting in the dog: a blinded crossover study

Nausea is a subjective sensation which is difficult to measure in non-verbal species. The aims of this study were to determine the efficacy of three classes of antiemetic drugs in a novel low dose cisplatin model of nausea and vomiting and measure change in potential nausea biomarkers arginine vasopressin (AVP) and cortisol. A four period cross-over blinded study was conducted in eight healthy beagle dogs of both genders. Dogs were administered 18 mg/m2 cisplatin intravenously, followed 45 min later by a 15 min infusion of either placebo (saline) or antiemetic treatment with ondansetron (0.5 mg/kg; 5-HT3 antagonist), maropitant (1 mg/kg; NK1 antagonist) or metoclopramide (0.5 mg/kg; D2 antagonist). The number of vomits and nausea associated behaviours, scored on a visual analogue scale, were recorded every 15 min for 8 h following cisplatin administration. Plasma samples were collected to measure AVP, cortisol and antiemetic drug concentrations

Breastfeeding patterns and exposure to suboptimal breastfeeding among children in developing countries: review and analysis of nationally representative surveys

BACKGROUND: Suboptimal breastfeeding is associated with higher mortality among infants and young children in the developing world. We describe patterns in 'exclusive breastfeeding' and 'any breastfeeding' rates and quantify exposure to suboptimal breastfeeding among children aged two years or younger in developing countries. METHODS: We reviewed nationally representative surveys that collected data on breastfeeding rates in 94 developing countries. Surveys were categorized by completeness and comprehensiveness of data. Complete and comprehensive data were analysed with minimum chi-square regression. With a fitting procedure, estimated parameters were used to impute missing observations for incomplete or non-comprehensive surveys. Breastfeeding indicators were calculated and are reported for 135 developing countries by UN region. RESULTS: Amongst infants aged six months or younger in the developing world, the prevalence of exclusive breastfeeding is 39% and the prevalence of no breastfeeding is 5.6%. The prevalence of continued breastfeeding is 86% and 68% for infants and children aged 6–11 and 12–23 months, respectively, in the developing world. Imputation expands population coverage of indicators, especially for infants. Breastfeeding trends are highly linear and estimated parameters defining the age-specific attrition hazard are robust. Survey-reported rates, particularly for exclusive breastfeeding, appear to have systematic upward bias, and exposure estimates must be considered conservative. CONCLUSIONS: Compliance with breastfeeding recommendations in developing countries is low, and more attention should be given to increasing breastfeeding – especially exclusive breastfeeding – and to monitoring trends. Although the introduction of more standardized and better validated survey instruments is desirable, since data coverage, completeness and comprehensiveness are extensive, global exposure assessment is relatively robust. Moreover, the regularity of breastfeeding patterns show existing survey data capture real biological and social phenomena. Our method for the analysis of breastfeeding rates provides a potent tool for summarizing trends, validating observations, translating and extrapolating indicators (as well as projecting and imputing estimates when necessary) and should support more effective child health monitoring

Intraoperative ultrasound-guided iodine-125 seed implantation for unresectable pancreatic carcinoma

<p>Abstract</p> <p>Background</p> <p>To assess the feasibility and efficacy of using ¹²⁵I seed implantation under intraoperative ultrasound guidance for unresectable pancreatic carcinoma.</p> <p>Methods</p> <p>Fourteen patients with pancreatic carcinoma that underwent laparotomy and considered unresectable were included in this study. Nine patients were pathologically diagnosed with Stage II disease, five patients with Stage III disease. Fourteen patients were treated with ¹²⁵I seed implantation guided by intraoperative ultrasound and received D₉₀of ¹²⁵I seeds ranging from 60 to 140 Gy with a median of 120 Gy. Five patients received an additional 35–50 Gy from external beam radiotherapy after seed implantation and six patients received 2–6 cycles of chemotherapy.</p> <p>Results</p> <p>87.5% (7/8) of patients received partial to complete pain relief. The response rate of tumor was 78.6%, One-, two-and three-year survival rates were 33.9% and 16.9%, 7.8%, with local control of disease achieved in 78.6% (11/14), and the median survival was 10 months (95% CI: 7.7–12.3).</p> <p>Conclusion</p> <p>There were no deaths related to ¹²⁵I seed implant. In this preliminary investigation, ¹²⁵I seed implant provided excellent palliation of pain relief, local control and prolong the survival of patients with stage II and III disease to some extent.</p

Adjuvant chemotherapy vs radiotherapy in high-risk endometrial carcinoma: results of a randomised trial

Patients with high-risk endometrial carcinoma (stage IcG3, IIG3 with myometrial invasion >50%, and III) receive adjuvant therapy after surgery but it is not clear whether radiotherapy (RT) or chemotherapy (CT) is better. We randomly assigned 345 patients with high-risk endometrial carcinoma to adjuvant CT (cisplatin (50 mg m−2), doxorubicin (45 mg m−2), cyclophosphamide (600 mg m−2) every 28 days for five cycles, or external RT (45–50 Gy on a 5 days week−1 schedule). The primary end points were overall and progression-free survival. After a median follow-up of 95.5 months women in the CT group as compared with the RT group, had a no significant hazard ratio (HR) for death of 0.95 (95% confidence interval (CI), 0.66–1.36; P=0.77) and a nonsignificant HR for event of 0.88 (95% CI, 0.63–1.23; P=0.45). The 3, 5 and 7-year overall survivals were 78, 69 and 62% in the RT group and 76, 66 and 62% in the CT group. The 3, 5 and 7-year progression-free survivals were, respectively, 69, 63 and 56 and 68, 63 and 60%. Radiotherapy delayed local relapses and CT delayed metastases but these trends did not achieve statistical significance. Overall, both treatments were well tolerated. This trial failed to show any improvement in survival of patients treated with CT or the standard adjuvant radiation therapy. Randomised trials of pelvic RT combined with adjuvant cytotoxic therapy compared with RT alone are eagerly awaited

The Influence of Direct and Indirect Speech on Mental Representations

Language can be viewed as a set of cues that modulate the comprehender's thought processes. It is a very subtle instrument. For example, the literature suggests that people perceive direct speech (e.g., Joanne said: 'I went out for dinner last night') as more vivid and perceptually engaging than indirect speech (e.g., Joanne said that she went out for dinner last night). But how is this alleged vividness evident in comprehenders' mental representations? We sought to address this question in a series of experiments. Our results do not support the idea that, compared to indirect speech, direct speech enhances the accessibility of information from the communicative or the referential situation during comprehension. Neither do our results support the idea that the hypothesized more vivid experience of direct speech is caused by a switch from the visual to the auditory modality. However, our results do show that direct speech leads to a stronger mental representation of the exact wording of a sentence than does indirect speech. These results show that language has a more subtle influence on memory representations than was previously suggested

Mechanism of action of the new anti-ischemia drug ranolazine

Myocardial ischemia is associated with reduced ATP fluxes and decreased energy supply resulting in disturbances of intracellular ion homeostasis in cardiac myocytes. In the recent years, increased persistent (late) sodium current was suggested to contribute to disturbed ion homeostasis by elevating intracellular sodium concentration with subsequent elevation of intracellular calcium. The new anti-ischemia drug ranolazine, a specific inhibitor of late sodium current, reduces sodium overload and hence ameliorates disturbed ion homeostasis. This is associated with symptomatic improvement of angina in patients. Moreover, ranolazine was shown to exhibit anti-arrhythmic effects. In the present article, we review the relevant pathophysiological concepts for the role of late sodium inhibition and summarize the most recent data from basic as well as clinical studies